Quantitative imaging system and uses thereof

Abstract

Provided herein are imaging systems such as a system for quantitative tomography and a laser optoacoustic ultrasonic imaging system assembly (LOUISA) for imaging a tissue region, for example, a breast, in a subject. Generally, the system components are a laser that emits instant pulses of laser light in a wavelength cycling mode, fiberoptic bundles or optical arc-shaped fiber bundles configured to deliver laser light, an imaging module with an imaging tank, an optoacoustic array(s) of ultrawide-band ultrasonic transducers and ultrasound array(s) of ultrasonic transducers and a coupling medium and an electronics subsystem. Also provided is a method for imaging quantitative functional parameters and/or molecular parameters and anatomical structures in a volumetric tissue region of interest, such as a breast, in a subject utilizing the system for quantitative tomography.

What is claimed is: 
     
       1. A laser optoacoustic ultrasonic imaging system assembly (LOUISA) for quantitative tomography, comprising:
 a pulsed laser configured to emit instant pulses of laser light at wavelengths within a red to near-infrared spectral range, said laser operable in a wavelength cycling mode with at least two different wavelengths; 
 a fiberoptic bundle that is configured to deliver the instant pulses of laser light to a volumetric tissue region of interest; 
 an imaging module comprising:
 an imaging tank shaped to accommodate a shape of the volumetric tissue region of interest; 
 at least one optoacoustic array of ultrawide-band ultrasonic transducers configured to detect ultrasonic signals within an ultrawide band of ultrasonic frequencies generated in the volumetric tissue region of interest by the instant pulses of laser light; 
 at least one ultrasound array of ultrasonic transducers configured to transmit pulses of ultrasound into the volumetric tissue region of interest and to detect ultrasonic signals reflected from or transmitted through the volumetric tissue region of interest; and 
 a coupling medium that fills the imaging tank and through which the instant pulses of laser light and the pulses of ultrasound are transmitted; 
 a multichannel electronic data acquisition system comprising analog preamplifiers, analog-to-digital converters and digital data storage, and processing and 
 
 a computer in electronic communication with the multichannel electronic data acquisition system and comprising a multicore central processing unit (CPU) and a multicore graphics processing unit (GPU) and tangibly storing software configured to control said CPU and GPU for system control, said software configured to enable processor-executable instructions for signal processing and image reconstruction and post-processing to produce images of quantitative molecular concentrations or functional parameters within the volumetric tissue region of interest, said instructions configured to:
 a. produce coregistered optoacoustic images acquired using at least two cycling laser wavelengths to obtain quantitative functional or molecular images; 
 b. for each image acquired at each wavelength in the cycle, restore original profiles of an optoacoustic signals generated in the volumetric tissue region by the instant laser pulses using deconvolution of acousto-electrical and spatial impulse response functions of the ultrawide-band ultrasonic transducer from the detected optoacoustic signals; 
 c. for each image acquired at each wavelength in the cycle, reconstruct 3D optoacoustic tomography images of the volumetric tissue region via rigorous direct algorithms or iterative algorithms utilizing complete data sets acquired in full view geometry; 
 d. for each image acquired at each wavelength in the cycle, normalize distribution of incident optical fluence on a surface of the volumetric tissue region by equalizing image brightness of all surface voxels with equal optical absorption; 
 e. for each image acquired at each wavelength in the cycle, normalize distribution of the optical fluence as a function of depth through the entire tissue region by measuring an effective optical attenuation from brightness of image voxels and compensating the image for effective optical attenuation via mathematical image processing; 
 f. for each image acquired at each wavelength in the cycle, produce and display images of an optical absorption coefficient after normalization of the optical fluence through the volumetric tissue region on optoacoustic images of the absorbed optical energy in the tissue region; and 
 g. use all coregistered images acquired at the at least two wavelengths in the cycle to produce a derivative image of quantitative molecular concentrations or functional parameters measured in the volumetric tissue region of interest; and 
 
 a high-resolution display electronically connected to the computer to present the reconstructed images to an operator to display quantitative molecular and functional information within anatomical tissue structures using co-registration of optoacoustic and ultrasonic images. 
 
     
     
       2. The laser optoacoustic ultrasonic imaging system assembly of  claim 1 , wherein the red and near-infrared spectral range of wavelengths is about 650 nm to about 1250 nm. 
     
     
       3. The laser optoacoustic ultrasonic imaging system assembly of  claim 1 , where in the laser is a chromium: lithium calcium hexafluoroaluminate (Cr:LiCAF) laser crystal. 
     
     
       4. The laser optoacoustic ultrasonic imaging system assembly of  claim 1 , wherein the wavelength cycling mode is two or three wavelengths within the red to near-infrared spectral range. 
     
     
       5. The laser optoacoustic ultrasonic imaging system assembly of  claim 4 , wherein the two cycling wavelengths are 757 nm and 850 nm. 
     
     
       6. The laser optoacoustic ultrasonic imaging system assembly of  claim 4 , wherein the three cycling wavelengths are 757 nm, 800 nm and 850 nm or 757 nm, 800 nm and 1064 nm. 
     
     
       7. The laser optoacoustic ultrasonic imaging system assembly of  claim 1 , wherein the ultrawide-band ultrasonic transducers in the array detect ultrasonic signals within an ultrawide band of 50 kHz to 6 MHz. 
     
     
       8. The laser optoacoustic ultrasonic imaging system assembly of  claim 1 , wherein the optoacoustic array of ultrawide-band ultrasonic transducers and the ultrasound array of ultrasonic transducers are combined into one array, or the optoacoustic array of ultrawide-band ultrasonic transducers is configured for both optoacoustic imaging and ultrasonic imaging. 
     
     
       9. The laser optoacoustic ultrasonic imaging system assembly of  claim 1 , wherein the ultrasound array of ultrasonic transducers is a laser ultrasound array comprising polymers with high thermal expansion and filled with strongly optically absorbing materials. 
     
     
       10. The laser optoacoustic ultrasonic imaging system assembly The system of  claim 1 , wherein the imaging tank in the imaging module has a spherical surface shape or a cylindrical surface shape. 
     
     
       11. The laser optoacoustic ultrasonic imaging system assembly of  claim 1 , wherein the volumetric tissue region of interest is a human breast, a human head or a small laboratory animal. 
     
     
       12. The laser optoacoustic ultrasonic imaging system assembly of  claim 1 , said instructions further configured to:
 transmit to the tissue region pulses of ultrasound from the ultrasound array; 
 detect with the ultrasound array signals reflected from or transmitted through the tissue region; 
 generate speed of sound images based on a distribution of speed of sound within the tissue region; 
 generate anatomical images of ultrasound reflection or attenuation from the detected ultrasonic signals; 
 coregister the anatomical images of ultrasound reflection, attenuation or speed of sound with quantitative functional or molecular images; and 
 display the coregistered images as an overlay of the images of quantitative functional parameters within the anatomical tissue structures or an overlay of the quantitative functional and molecular images and speed of sound images. 
 
     
     
       13. The laser optoacoustic ultrasonic imaging system assembly of  claim 1 , wherein the system is a laser optoacoustic ultrasonic imaging system for imaging a breast in a subject, comprising:
 the pulsed laser; 
 the fiberoptic bundle that is arc-shaped and configured to rotate around the breast in steps to deliver the instant pulses of laser light at each step to the breast; 
 the imaging tank with a spherical surface shape corresponding to the breast; 
 the at least one optoacoustic array of ultrawide-band ultrasonic transducers, wherein said optoacoustic array is an arc-shaped 1.5D or 2D array that is configured to detect ultrasonic signals within an ultrawide band of at least 50 KHz to at least 6 MHz generated in the breast by the instant pulses of laser light; 
 the at least one ultrasound array of ultrasonic transducers, wherein said ultrasound array is an arc-shaped 1.5D or 2D array that is configured to transmit pulses of ultrasound into the breast and to detect ultrasonic signals reflected from or transmitted through the breast, said ultrasound array optionally combined with the optoacoustic 1.5D or 2D array in one housing or is one array with the optoacoustic 1.5D or 2D array; 
 the coupling medium that is optically and acoustically transparent; and 
 in an electronic subsystem
 the multichannel electronic data acquisition system; 
 the computer in electronic communication with the multichannel electronic data acquisition system; 
 the software tangibly stored on the computer and configured to enable the processor-executable instructions; and 
 the high-resolution display electronically connected to the computer. 
 
 
     
     
       14. The laser optoacoustic ultrasonic imaging system assembly of  claim 13 , wherein the pulsed laser is operable at two cycling wavelengths of 757±5 nm and 850±10 nm. 
     
     
       15. The laser optoacoustic ultrasonic imaging system assembly of  claim 13 , wherein the pulsed laser is operable at three cycling wavelengths of 757±5 nm, 800±5 nm and 850±10 nm or 757±5 nm, 800±5 nm and 1064±10 nm. 
     
     
       16. The laser optoacoustic ultrasonic imaging system assembly of  claim 13 , wherein the optoacoustic array of ultrawide ultrasonic transducers and the ultrasound array of ultrasonic transducers are combined into one array. 
     
     
       17. The laser optoacoustic ultrasonic imaging system assembly of  claim 13 , wherein the fiberoptic bundle, the optoacoustic array and the ultrasound array are configured to independently rotate around the breast for illumination of the entire breast for each position of the optoacoustic array and the ultrasound array. 
     
     
       18. The laser optoacoustic ultrasonic imaging system assembly of  claim 13 , wherein a patient examination is made on a platform that moves from a vertical position to a horizontal position, and an imaging module is placed on a computer controlled three-dimensional translation stage, enabling a patient breast scan without patient movement on the platform. 
     
     
       19. The laser optoacoustic ultrasonic imaging system assembly of  claim 1 , wherein the fiberoptic bundle comprises a hot-fused input tip for maximum optical transmission and an output to enable beam homogeneity on a surface of the volumetric tissue region of interest. 
     
     
       20. A method for imaging quantitative or functional parameters in a volumetric tissue region of interest in a subject with enhanced resolution and accuracy using image of the speed of sound, comprising the steps of:
 placing the volumetric tissue region in the imaging tank of the LOUISA system of  claim 1 ; 
 generating images of quantitative functional parameters or molecular parameters from the coregistered optoacoustic images; 
 acquiring images of speed of sound distribution within the tissue region; 
 using images of the speed of sound to improve contrast and resolution of coregistered optoacoustic images or quantitative functional and molecular images; and 
 displaying the generated images with enhanced resolution and quantitative accuracy. 
 
     
     
       21. The method of  claim 20 , further comprising:
 enhancing the resolution of ultrasound reflection or attenuation images using maps of the speed of sound images. 
 
     
     
       22. The method of  claim 20 , further comprising:
 detecting at least one cancerous tumor and differentiating it from a noncancerous tumor using coregistered images of the quantitative functional parameters or the molecular parameters displayed within anatomical structures in the overlay of optoacoustic and ultrasonic images. 
 
     
     
       23. The method of  claim 22 , wherein the cancerous tumor is a cancerous breast tumor. 
     
     
       24. The method of  claim 20 , wherein acquiring ultrasound images occurs between acquiring optoacoustic images at cycling wavelengths. 
     
     
       25. The method of  claim 20 , wherein the quantitative functional parameter comprises a concentration of a protein, of a protein receptor or of a molecule associated with a cancer or a combination thereof. 
     
     
       26. The method of  claim 20 , wherein the functional parameter is total hemoglobin [tHb] or blood oxygen saturation [sO2] or a combination thereof.